Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab

August 12, 2026 updated by: RAPT Therapeutics, Inc.

Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer

This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.

The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

323

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Linear Clinical Research Limited
  • Hong Kong
      • High West, Hong Kong
        • Queen Mary Hospital
      • High West, Hong Kong
        • Queen Mary Hospital - Lymphoma
      • Shatin, Hong Kong
        • Prince of Wales Hospital
  • South Korea
      • Seoul, South Korea, 05505
        • Asan Medical Center
      • Seoul, South Korea, 06351
        • Samsung Medical Center
      • Seoul, South Korea, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea, 03080
        • Seoul National University
      • Taebuk, South Korea, 28644
        • Chungbuk National University Hospital
  • Taiwan
      • Tainan, Taiwan, 70403
        • National Cheng Kung University Hospital
      • Tainan, Taiwan, 71004
        • Chi Mei Meidcal Center
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
  • Thailand
      • Bangkok, Thailand, 10400
        • Ramathibodi Hospital
      • Bangkok, Thailand, 10330
        • King Chulaongkorn Memorial Hospital
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • Los Angeles, California, United States, 90024
        • University of California, Los Angeles JCCC Clinical Research Unit
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Cancer Center
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown - Lombardi Comprehensive Cancer Center
    • Florida
      • St. Petersburg, Florida, United States, 33709
        • Comprehensive Hematology and Oncology, LLC
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Hospital/James Graham Brown Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
        • Quantum Santa Fe
    • New York
      • New York, New York, United States, 10032
        • New York Presbyterian Hospital-Columbia University Medical Center
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Carolina Biooncology Institute
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research Center
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies

    • Dose Escalation: non-small cell lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, metastatic triple negative breast cancer, urothelial carcinoma, gastric cancer, esophageal carcinoma, cervical cancer, classical Hodgkin lymphoma
    • Dose Expansion: nasopharyngeal carcinoma, lymphoma, head and neck squamous cell carcinoma, cervical cancer, non-small cell lung cancer, triple-negative breast cancer
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)
  • Tumor available for biopsy

Exclusion Criteria:

  • History of allergy or severe hypersensitivity to biologic agents
  • History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment
  • Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis
  • Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant
  • Active graft-versus-host disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1a: Monotherapy Dose Escalation
Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.
Drug: FLX475 (tivumecirnon)
tablet
Experimental: Part 1b: Combination Dose Escalation
Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.
Drug: pembrolizumab (KEYTRUDA®)
IV infusion
Drug: FLX475 (tivumecirnon)
tablet
Experimental: Part 2a: Monotherapy Expansion Cohorts
Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2.
Drug: FLX475 (tivumecirnon)
tablet
Experimental: Part 2b: Combination Expansion Cohorts
Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.
Drug: pembrolizumab (KEYTRUDA®)
IV infusion
Drug: FLX475 (tivumecirnon)
tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of FLX475 as a Single Agent and in Combination With Pembrolizumab Measured by the Incidence of Adverse Events, Including Dose-limiting Toxicities and Maximum Tolerated Dose
Time Frame: Approximately 18 weeks
treatment-emergent adverse events
Approximately 18 weeks
Overall Response Rate in Subjects Treated With FLX475 as a Single Agent and in Combination With Pembrolizumab
Time Frame: Through study completion (approximately 2 years)
Summary of Best Overall Response
Through study completion (approximately 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RAPT Therapeutics, Inc.

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: William Ho, MD, PhD, RAPT Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2018

Primary Completion (Actual)

December 31, 2024

Study Completion (Actual)

December 31, 2024

Study Registration Dates

First Submitted

September 14, 2018

First Submitted That Met QC Criteria

September 14, 2018

First Posted (Actual)

September 17, 2018

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

August 12, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FLX475-02
  • KEYNOTE-877 (Other Identifier: Merck Sharp & Dohme LLC)
  • MK-3475-877 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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